Cyclic Peptides as Protein Kinase Inhibitors: Structure-Activity Relationship and Molecular Modeling.

Under-expression or overexpression of protein kinases has been shown to be associated with unregulated cell signal transduction in cancer cells. Therefore, there is major interest in designing protein kinase inhibitors as anticancer agents. We have previously reported [WR], a peptide containing alternative arginine (R) and tryptophan (W) residues as a non-competitive c-Src tyrosine kinase inhibitor.

Comparative Molecular Transporter Efficiency of Cyclic Peptides Containing Tryptophan and Arginine Residues.

Cyclic peptides containing tryptophan (W) and arginine (R) residues, [WR], [WR], [WR], [WR], and [WR], were synthesized through Fmoc solid-phase chemistry to compare their molecular transporter efficiency. The in vitro cytotoxicity of the peptides was evaluated using human leukemia carcinoma cell line (CCRF-CEM) and normal kidney cell line (LLC-PK1). [WR], [WR], [WR], and [WR] were not significantly cytotoxic to LLC-PK1cells at a concentration of 10 μM after 3 h incubation.